Pro-Tumorigenic Macrophage Infiltration in Oral Squamous Cell Carcinoma and Possible Macrophage-Aimed Therapeutic Interventions

Bruna, Flavia; Scodeller, Pablo

doi:10.3389/fonc.2021.675664

Cited by 10 publications

(7 citation statements)

References 103 publications

(140 reference statements)

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“…However, a recent meta-analysis showed no association between CD8 infiltration and survival in oral cancer [ 30 ]. The infiltration of tumor-associated CD68-positive macrophages and, in particular, tumor-promoting, M2-polarized, CD163-expressing macrophages was shown to be associated with oral cancer initiation and tumor progression [ 31 , 32 , 33 ]. Nevertheless, although cancer-associated fibroblasts (CAFs) are important stromal cells, the characterization of their heterogeneity is far from complete.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, CD115 is expressed by a heterogeneous myeloid cell population with immune-suppressive properties, designated myeloid-derived suppressor cells (MDSCs) [ 35 ]. IL-10 is a major immune-suppressive cytokine secreted by MDSCs [ 36 ], M2 macrophages [ 31 ] and T reg cells [ 37 ]. Figure 1 displays an overview of the analyzed cell populations and cytokines in the current study.…”

Section: Introductionmentioning

confidence: 99%

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Beyond PD-L1—Identification of Further Potential Therapeutic Targets in Oral Cancer

Weber

Lutz

Olmos

et al. 2022

Cancers

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Background: The involvement of immune cell infiltration and immune regulation in the progression of oral squamous cell carcinoma (OSCC) is shown. Anti-PD-1 therapy is approved for the treatment of advanced OSCC cases, but not all patients respond to immune checkpoint inhibitors. Hence, further targets for therapeutic approaches are needed. The number of identified cellular receptors with immune checkpoint function is constantly increasing. This study aimed to perform a comparative analysis of a large number of immune checkpoints in OSCC in order to identify possible targets for therapeutic application. Materials and Methods: A NanoString mRNA analysis was performed to assess the expression levels of 21 immune regulatory checkpoint molecules in OSCC tissue (n = 98) and healthy oral mucosa (NOM; n = 41). The expression rates were compared between the two groups, and their association with prognostic parameters was determined. Additionally, relevant correlations between the expression levels of different checkpoints were examined. Results: In OSCC tissue, significantly increased expression of CD115, CD163, CD68, CD86, CD96, GITRL, CD28 and PD-L1 was detected. Additionally, a marginally significant increase in CD8 expression was observed. BTLA and PD-1 levels were substantially increased, but the differential expression was not statistically significant. The expression of CD137L was significantly downregulated in OSCC compared to NOM. Correlations between immune checkpoint expression levels were demonstrated, and some occurred specifically in OSCC tissue. Conclusions: The upregulation of inhibitory receptors and ligands and the downregulation of activators could contribute to reduced effector T-cell function and could induce local immunosuppression in OSCC. Increased expression of activating actors of the immune system could be explained by the increased infiltration of myeloid cells and T-cells in OSCC tissue. The analysis contributes to the understanding of immune escape in OSCC and reveals potential targets for oral cancer immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Beyond PD-L1—Identification of Further Potential Therapeutic Targets in Oral Cancer

Weber

Lutz

Olmos

et al. 2022

Cancers

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“…However, tumor-associated macrophages (TAMs) infiltrate into the tumors and differentiate into mature protumor macrophages (M1 and M2 macrophages) mediated by cytokines in the TME (99)(100)(101). Although the pro-tumorigenic role of M1 is context dependent based on tumor microenvironmental cues (102,103). Macrophages also show phagocytotic activity toward damaged tumor cells (104).…”

Section: Autophagy and Reactive Oxygen Species In Cancer: A Promoter ...mentioning

confidence: 99%

Crosstalk Between ROS and Autophagy in Tumorigenesis: Understanding the Multifaceted Paradox

et al. 2022

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Cancer formation is a highly regulated and complex process, largely dependent on its microenvironment. This complexity highlights the need for developing novel target-based therapies depending on cancer phenotype and genotype. Autophagy, a catabolic process, removes damaged and defective cellular materials through lysosomes. It is activated in response to stress conditions such as nutrient deprivation, hypoxia, and oxidative stress. Oxidative stress is induced by excess reactive oxygen species (ROS) that are multifaceted molecules that drive several pathophysiological conditions, including cancer. Moreover, autophagy also plays a dual role, initially inhibiting tumor formation but promoting tumor progression during advanced stages. Mounting evidence has suggested an intricate crosstalk between autophagy and ROS where they can either suppress cancer formation or promote disease etiology. This review highlights the regulatory roles of autophagy and ROS from tumor induction to metastasis. We also discuss the therapeutic strategies that have been devised so far to combat cancer. Based on the review, we finally present some gap areas that could be targeted and may provide a basis for cancer suppression.

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“…HNSCC cells polarized monocytes into M2-like macrophages resulting in the promotion of HNSCC cell migration via the secretion of epithelial growth factor (EGF) [ 11 ]. In the OSCC microenvironment, OSCC cells secrete cytokines or chemokines to regulate the activities of macrophages [ 12 , 13 ]. Infiltrated macrophages also interact with cancer cells to promote tumor progression in a paracrine manner [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between cancer cells and macrophages promotes OSCC cell migration and invasion through a CXCL1/EGF positive feedback loop

Huang,

Jiang,

Lin

et al. 2024

Discov Onc

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Background C-X-C motif chemokine ligand 1 (CXCL1) and epithelial growth factor (EGF) are highly secreted by oral squamous cell carcinoma (OSCC) cells and tumor-associated macrophages, respectively. Recent studies have shown that there is intricate "cross-talk" between OSCC cells and macrophages. However, the underlying mechanisms are still poorly elucidated. Methods The expression of CXCL1 was detected by immunohistochemistry in OSCC clinical samples. CXCL1 levels were evaluated by RT‒PCR and ELISA in an OSCC cell line and a normal epithelial cell line. The expression of EGF was determined by RT‒PCR and ELISA. The effect of EGF on the proliferation of OSCC cells was evaluated by CCK-8 and colony formation assays. The effect of EGF on the migration and invasion ability and epithelial-mesenchymal transition (EMT) of OSCC cells was determined by wound healing, Transwell, RT‒PCR, Western blot and immunofluorescence assays. The polarization of macrophages was evaluated by RT‒PCR and flow cytometry. Western blotting was used to study the molecular mechanism in OSCC. Results The expression of C-X-C motif chemokine ligand 1 (CXCL1) was higher in the OSCC cell line (Cal27) than in immortalized human keratinocytes (Hacat cells). CXCL1 derived from Cal27 cells upregulates the expression of epithelial growth factor (EGF) in macrophages. Paracrine stimulation mediated by EGF further facilitates the epithelial-mesenchymal transition (EMT) of Cal27 cells and initiates the upregulation of CXCL1 in a positive feedback-manner. Mechanistically, EGF signaling-induced OSCC cell invasion and migration can be ascribed to the activation of NF-κB signaling mediated by the epithelial growth factor receptor (EGFR), as determined by western blotting. Conclusions OSCC cell-derived CXCL1 can stimulate the M2 polarization of macrophages and the secretion of EGF. Moreover, EGF significantly activates NF-κB signaling and promotes the migration and invasion of OSCC cells in a paracrine manner. A positive feedback loop between OSCC cells and macrophages was formed, contributing to the promotion of OSCC progression.

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Pro-Tumorigenic Macrophage Infiltration in Oral Squamous Cell Carcinoma and Possible Macrophage-Aimed Therapeutic Interventions

Cited by 10 publications

References 103 publications

Beyond PD-L1—Identification of Further Potential Therapeutic Targets in Oral Cancer

Beyond PD-L1—Identification of Further Potential Therapeutic Targets in Oral Cancer

Crosstalk Between ROS and Autophagy in Tumorigenesis: Understanding the Multifaceted Paradox

Crosstalk between cancer cells and macrophages promotes OSCC cell migration and invasion through a CXCL1/EGF positive feedback loop

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